Hypercholesterolemia Drugs Flashcards
Which cholesterols cause and inhibit hyperlipidemia?
LDL promotes hyperlipidemia. HDL inhibits hyperlipidemia. Triglycerides promote hyperlipidemia in an unclear way
What are the “good” and “bad” cholesterols?
LDL = bad (Lousy) HDL = good (Happy)
Describe the basic structure of an LDL
Spherical shape.
Phospholipids and cholesterol on the outside along with apoprotein B100. On the inside of the sphere, there are triglycerides and cholesterol esters
What enzyme cleaves fatty acids from chylomicrons in the bloodstream?
Lipoprotein Lipase (LPL)
Where are released fatty acids taken up?
Free fatty acids taken up by adipose tissue (storage) or by muscle (energy production through Beta-oxidation)
Describe the very basic mechanism of atherosclerosis as caused by hyperlipidemia
High LDL infiltrates the vessel wall, leading to development of an atheroma (fatty streak) to cause atherosclerosis
What happens to the LDLs when they enter the intima?
They get oxidized.
What does the oxidation of LDLs cause?
Upregulation of adhesion molecules on the endothelium, leading to monocyte infiltration of the intima
When macrophages swallow LDL, they become….
Foam cells
How do foam cells function?
Secrete growth factors and ECM components. Allows medial smooth muscle to infiltrate into the intima through the IEL. Forms an artherosclerotic plaque!
Describe the protective functions of HDL in prevention of atherosclerosis
Inhibits oxidation of LDLs (PON1 on HDLs has antioxidant activity)
Inhibit adhesion molecule expression on endothelium
Inhibit foam cell formation
Promotes reverse cholesterol transport (from the periphery to the liver to be secreted as bile)
List some causes of Hyperlipidemia
Genetics (Familial Hyperlipidemia -- defect in LDL receptor) High fat/carb diet Age Physical inactivity Alcohol consumption Smoking Diabetes Drugs (HIV antiviral proteases, antipsychotics)
What is the ideal serum level of LDL?
Less than 100mg/dL
What is a very high serum LDL level?
> 190 mg/dL
What is an ideal serum triglyceride level?
Less than 150mg/dL
What is a very high serum triglyceride level?
> 500 mg/dL
Very high serum triglyceride levels increase a patient’s risk of developing…
Pancreatitis
What is the principal goal of treatment for hypercholesterolemia?
Reduce serum LDL levels to hopefully reduce risk of cardiovascular disease
Statins inhibit what enzyme? What does this accomplish?
HMG CoA Reductase
Reduction of serum LDLs
Describe the mechanism by which statins lower LDL levels
Bind HMG CoA reductase and competitively inhibit it. Triggers a signaling pathway that activates SREBP transcription factor to upregulate LDL receptors in cells. Increase LDL uptake from the serum, therefore decreasing serum levels. The LDL’s cholesterol can be excreted in bile
What are some other anti-atherogenic effects of statins?
- Inhibit adhesion molecules on the endothelium.
- Inhibit foam cell production.
- Inhibit smooth muscle proliferation.
- Anti-inflammatory
Does a statin’s ability to decrease CV disease risk depend on LDL levels?
No! Statins decrease risk of CV diseases even in patients with normal LDL levels.
Does increasing the dose of a statin generally cause a greater reduction in LDL?
Not really. Increasing the dose doesn’t have much effect in reducing LDLs, but increased statin dose increases risk of adverse effects
Adverse Effects of Statins
Generally well tolerated.
- Mild GI disturbance
- Increase liver enzymes
- Increase risk of T2DM
- Myalgia/Myopathy
- Rhabdomyolysis
